Although the polyether antibiotics were first described more than twenty-five years ago, the therapeutic potential of this antibiotic class was not appreciated until 1968 when the anticoccidial activity of monensin was reported. The subsequent commercial use of monensin for the treatment of avian coccidiosis and its development as a growth promoter in cattle led to the realization that other members of the class, including nigericin, lasalocid, salinomycin, laidlomycin and lonomycin also have therapeutic potential.
Utilization of these agents in agriculture as feed additives for the treatment of disease in poultry and for the enhancement of growth in ruminants requires that they be available at a relatively low cost. Thus, the fermentation must be capable of producing the antibiotic in high yield and, in addition, isolation of product must be conducted simply and efficiently. The published procedures for the isolation of polyether antibiotics are multistep operations involving column chromatography.
Thus, for example, U.S. Pat. No. 3,873,693 to Meyers et al discloses the antibiotic ionomycin and a technique for recovering same from the fermentation broth by filtering off the mycelium, extracting the filtrate with a lower alkanol like butanol, or a lower alkyl ester like ethyl acetate or butyl acetate, or a hydrocarbon like chloroform or a lower alkyl ketone like methyl isobutyl ketone. The organic phase is concentrated to a syrup; the purified product is obtained by column chromatography.
Omura et al in a paper entitled "Isolation of a New Polyether Antibiotic, Lonomycin", J. Antibiotics, XXIX No. 1 (1976), pp 15-20, describe a technique for isolation and purification of lonomycin as follows. The mycelia is centrifuged from the fermentation broth and extracted with ethyl acetate. The ethyl acetate extract is separated from the aqueous layer and concentrated in vacuo below 50.degree. C. to give a brown syrup. The syrup is extracted three times with benzene. The resulting extract is recovered, evaporated to dryness, and the residue is extracted three times with methanol. The extracts are concentrated in vacuo to give a partially purified antibiotic in the form of a yellow syrup. The syrup is dissolved in benzene and subjected to column chromatography to give a white powder which is recrystallized from n-hexane to give lonomycin.
Similar expensive and time-consuming multistep isolation procedures including column chromatography are required in the recovery of monensin and other polyether antibiotics from fermentation broths.
Thus, it is seen that a long felt need exists for a simple, efficient method for isolating polyether antibiotics of high purity.